Anti-Atherosclerotic Effect of Hibiscus Leaf Polyphenols against Tumor Necrosis Factor-alpha-Induced Abnormal Vascular Smooth Muscle Cell Migration and Proliferation

Abstract

The proliferation and migration of vascular smooth muscle cells (VSMCs) are major events in the development of atherosclerosis following stimulation with proinflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Plant-derived polyphenols have attracted considerable attention in the prevention of atherosclerosis. Hibiscus leaf has been showed to inhibit endothelial cell oxidative injury, low-density lipoprotein oxidation, and foam cell formation. In this study, we examined the anti-atherosclerotic effect of Hibiscus leaf polyphenols (HLPs) against abnormal VSMC migration and proliferation in vitro and in vivo. Firstly, VSMC A7r5 cells pretreated with TNF-α were demonstrated to trigger abnormal proliferation and affect matrix metalloproteinase (MMP) activities. Non-cytotoxic doses of HLPs abolished the TNF-α-induced MMP-9 expression and cell migration via inhibiting the protein kinase PKB (also known as Akt)/activator protein-1 (AP-1) pathway. On the other hand, HLP-mediated cell cycle G0/G1 arrest might be exerted by inducing the expressions of p53 and its downstream factors that, in turn, suppress cyclin E/cdk2 activity, preventing retinoblastoma (Rb) phosphorylation and the subsequent dissociation of Rb/E2F complex. HLPs also attenuated reactive oxygen species (ROS) production against TNF-α stimulation. In vivo, HLPs improved atherosclerotic lesions, and abnormal VSMC migration and proliferation. Our data present the first evidence of HLPs as an inhibitor of VSMC dysfunction, and provide a new mechanism for its anti-atherosclerotic activity.

10-HDA Induces ROS-Mediated Apoptosis in A549 Human Lung Cancer Cells by Regulating the MAPK, STAT3, NF-κB, and TGF-β1 Signaling Pathways

“…The cyclin D1 gene, which is tightly correlated with cancerous cell proliferation, has been considered a marker molecule [ 36 ]. Similarly, cyclin E and CDK2/4/6 also play key roles in the G0/G1 transition in the cell cycle [ 37 – 40 ]. Furthermore, p21 and p27 act by binding CDK in the G1 phase of the cell cycle, leading to inhibition of the phosphorylation of other proteins such as retinoblastoma, which is necessary for cell cycle progression [ 41 , 42 ].…”

Immunomodulatory and Mechanistic Considerations of Hibiscus sabdariffa (HS) in Dysfunctional Immune Responses: A Systematic Review

“…Administration of HS calyces extract significantly decreased the levels of different pro-inflammatory biomarkers such as TNF-α ( 9 , 11 , 16 , 31 , 40 – 43 ), Interleukin 6 (IL-6) ( 11 , 16 , 17 , 40 , 42 – 44 ), iNOS ( 31 , 45 ), Toll-like receptor 4 (TLR4) ( 16 ), Interleukin 1β (IL-1β) ( 9 , 16 , 42 ), MCP-1 ( 11 , 16 , 42 ), Ang I ( 46 ), Ang II ( 26 ), ACE1 ( 24 – 26 , 47 ), NF-κB ( 17 ), and Cyclooxygenase-2 (COX-2) ( 38 , 48 ). It also significantly decreased the levels of inflammatory manifestations of ear edema ( 1 , 49 ) and paw edema ( 11 ).…”

Preparative HPLC fraction of Hibiscus rosa-sinensis essential oil against biofilm forming Klebsiella pneumoniae

“…Other promoter and various factors could modify chemical components including soil, fertility, pH, temperature, humidity and other stresses ( Kandhare et al, 2012 , Da-Costa-Rocha et al, 2014 ). Previously Malinowski et al, 2019 , Chou et al, 2019 , reported that the EO production depends on the seasonal variation and various environmental factors. It also increases the common volatile compounds natures due to the stress condition.…”